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SRP102360
Mus musculus
16 Downloadable Samples
Illumina HiSeq 2500
Description
Using a mouse model overexpressing human SNCA and profiling the hippocampal transcriptome, we assessed gene-environment interactions to reveal perturbations in gene expression and their modulation through long-term enriched environment (EE) exposure. We observed that EE prevented perturbations of genes attributed to neuronal and glial cell types and linked to glutamate signaling, calcium homeostasis, inflammation, and related processes of SNCA biology. Cluster and promoter analyses suggested driver genes that specifically responded to the EE, and pointed to a pivotal role of Egr1 to have hierarchically activated other drivers. We suggest a model in which EE-induced driver genes prevent and counter-balance perturbations of SNCA overexpression, restoring a largely normalized gene expression profile and system state. Overall design: Using a 2x2 factorial design, we cross-compared a line of transgenic mice overexpressing human SNCA with wildtype animals, and the effects of a long-term EE with standard housing conditions. Employing RNA-seq, we profiled gene expression in the hippocampus of 12-month-old female animals.
Publication Title
Environmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the developing heart, heterotypic transcription factors (TFs) interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5 have been proposed as a mechanism for human congenital heart disease. In order to study the role of each TF during heart formation, embryonic stem (ES) cell-derived embryos were generated from KO ES cells for Tbx5, Nkx2-5 or both TFs.
Publication Title
Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
The ability to generate defined null mutations in mice revolutionized the analysis of gene function in mammals. However, gene-deficient mice generated by using 129-derived embryonic stem (ES) cells may carry large segments of 129 DNA, even when extensively backcrossed to reference strains, such as C57BL/6J, and this may confound interpretation of experiments performed in these mice. Tissue plasminogen activator (tPA), encoded by the PLAT gene, is a fibrinolytic serine protease that is widely expressed in the brain. A large number of neurological abnormalities have been reported in tPA-deficient mice. The studies here compare genes differentially expressed in the brains of Plat-/- mice from two independent Plat-/- mouse derivations to wild-type C57BL/6J mice. One strain denoted “Old” was constructed in ES cells from a 129 mouse and backcrossed extensively to C57BL/6J, and one denoted “New” Plat-/- mouse was constructed using zinc finger nucleases directly in the C57BL/6J-Plat-/- mouse strain. We identify a significant set of genes that are differentially expressed in the brains of Old Plat-/- mice that preferentially cluster in the vicinity of Plat on chromosome 8, apparently linked to more than 20 Mbp of DNA flanking Plat being of 129 origin. No such clustering is seen in the New Plat-/- mice. Overall design: Whole-transcriptome profiling of the cerebral cortex of wild-type control C57BL/6J mice and two independent Plat-/- mice strains on the C57BL/6J background.
Publication Title
Passenger mutations and aberrant gene expression in congenic tissue plasminogen activator-deficient mouse strains.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
We are investigating the transcriptional response of yeast to treatment with enediynes or gamma radiation, which generate different extents of double or single strand breaks in DNA.
Publication Title
The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
We are investigating the transcriptional response of Anc1 deficient yeast under basal and MMS exposed conditions
Publication Title
Anc1, a protein associated with multiple transcription complexes, is involved in postreplication repair pathway in S. cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Overall design: Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates
Publication Title
RNA-Seq of human breast ductal carcinoma in situ models reveals aldehyde dehydrogenase isoform 5A1 as a novel potential target.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Homo sapiens
- 198 Downloadable Samples
- IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. However, post-transcriptional mechanisms involved in mRNA processing have been poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Overall design: Transcriptomic profiles of 198 infected (Listeria and Salmonella) and non-infected samples at multiple time points.
Publication Title
Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription factor Foxp3 is indispensable for the ability of regulatory T (Treg) cells to suppress fatal inflammation. Here, we characterized the role of Foxp3 in chromatin remodeling and regulation of gene expression in actively suppressing Treg cells in an inflammatory setting. Although genome-wide Foxp3 occupancy of DNA regulatory elements was similar in resting and in vivo activated Treg cells, Foxp3-bound enhancers were poised for repression only in activated Treg cells. Following activation, Foxp3-bound sites showed reduced chromatin accessibility and selective H3K27 tri-methylation, which was associated with Ezh2 recruitment and downregulation of nearby gene expression. Thus, Foxp3 poises its targets for repression by facilitating formation of repressive chromatin in regulatory T cells upon their activation in response to inflammatory cues.
Publication Title
Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples